This grant application focuses upon the stress biology of mood and anxiety disorders and will provide key neuroendocrine data to test models of anxiety and depression and the co-morbid state proposed in the Specific Aims. Current research indicates that depression is accompanied by abnormalities of the HPA axis, while anxiety disorders, particularly panic disorder, is accompanied by abnormalities of the central NA system, as reflected by a blunted growth hormone (GH) response to clonidine. Specific research aims in this application are: 1) to determine if abnormalities of central NA system are present in both pure depression, pure panic disorder and depression plus panic disorder. The investigator will study a group of well characterized pure depressed, pure panic and mixed panic and depressed patients with the clonidine/GH challenge to determine if all depressed patients manifest abnormalities in clonidine stimulated GH release or if only those with co-morbid panic symptoms manifest this abnormality. 2) To determine if abnormal activation of HPA axis secretion occurs in Panic Disorder patients as well as in depressed patients. The investigator will examine 24 hour urinary-free cortisol (UFC) excretion, collected in 8 hour segments in pure depressed, pure panic and mixed panic and depressed patients. 3) To evaluate NA and HPA axis "reactivity" to two simple challenges in pure depression, depression plus anxiety, panic disorder patients and normal controls. These challenges are orthostatic challenge and the Trier Social Stress Test (TSST). The investigator hypothesizes that panic disorder patients and depressed patients with co-morbid anxiety will demonstrate exaggerated catecholamine response to orthostatic challenge, i.e., increased reactivity. The investigator hypothesizes that depressed patients will have altered HPA axis responses to stress while panic disorder patients will have normal HPA axis response to the TSST. 4) To determine if basal HPA axis regulation, responses to stressor and response to clonidine-GH challenge are correlated within individuals and if the relationship between these two systems (HPA and catecholamine) is altered by disease state. Finally, the investigator will evaluate the hypothesis that HPA axis and NA dysfunction reflect a common factor, degree of impairment, more than a specific mood and anxiety disorder. The results of these studies will provide data on whether the biology of these disorders support the nosological distinction between panic disorder, pure major depression and major depression with co-morbid panic disorder.